14 MUTATIONS 



make a preliminary crude guess as to which of these situations applies. 

 This has been considered with two different results. First, in chondro- 

 dystrophy, there is a strong dependence on the age of the father. 

 Vogel (42) grouped available data to compare ages of less than 30 

 with ages of over 35; the difference in mutation rates to dominant 

 chondrodystrophy between these age groups is said to be about a 

 factor of 3.8. 



Auerbach: Is this corrected for the age of the mother? 



Atwood: Yes. That is hard to unscramble, but it was done. 



Demerec: Is that done over a large number of mutations? 



Atwood: I don't know; some have argued that dominant chondro- 

 dystrophy has more than one locus involved. 



Neel: A point here is that of all the achondroplastic infants born, 

 only about 20 per cent survive beyond the first year of life. Vogel's 

 figure is based entirely, as I recall it, on that 20 per cent. 



Atwood: The lethal form of it might be a different locus, too. 



Neel: Which is not age dependent. Certainly, the age effect in 

 achondroplasia far exceeds that known for such other mutants as 

 neurofibromatosis or retinoblastoma. I don't think we can generalize 

 from this. 



Atwood: In any case, if you pick some convenient points, say, age 

 40 and 25, and assume that these are the mean ages of Vogel's two 

 groups, and then extrapolate back the slope that you get from the 

 factor of 3.8 difference between ages 25 and 40, you find that you come 

 out with a negative value at birth, a very large negative value, which 

 shows that the rate of increase of the mutant gametes with age is high, 

 and not only that, but it shows that the rate is increasing with age. 



Auerbach: There could be some discontinuity, couldn't there? Per- 

 haps the chemical environment of the spermatozoa in an old father acts 

 in a mutagenic way. 



Atwood: Possibly, in any case, the apparent increase with age is 

 not linear; it accelerates. 



Neel: As I recall it, for neurofibromatosis and for aniridia the aver- 

 age father of a presumably mutant child is about a half year older 

 than the population average. I think that would be a little better 

 time interval to work with than the achondroplasia interval. 



Atwood: Well, Vogel gives the same or a comparable figure for the 

 things you mentioned; that is, aniridia, neurofibromatosis, and one 

 other, which I don't remember. 



Neel: Retinoblastoma? 



Atwood: Yes. Now, for these, the factor was 1.26, and if you use 



